Mechanisms of sylvatic dengue emergence
Sarawak study collaborators (from left): David Perera, Jane Cardosa, Katherine Bossart, Kathryn Hanley, Nik Vasilakis, Katie Young and Fiona McCrossin (Brenda Benefit, photographer) Large View
The four serotypes of mosquito-borne dengue virus, which infect up to 100 million people worldwide each year, are the agents of dengue fever. Dengue virus is unique among arthropod-borne viruses in that humans serve as the reservoir host for the virus. Nonetheless each of the four serotypes initially emerged into humans from an ancestral, sylvatic cycle between non-human primates, and perhaps other reservoir species, and arboreal Aedes mosquitoes. This cycle is still extant in southeast Asia and West Africa.
West Africa: In conjunction with collaborators at the University of Texas, Institut Pasteur Senegal, Johns Hopkins, the Santa Fe Institute and New Mexico State University, we have initiated a field study in Kedougou, Senegal, in order to understand the mechanisms by which dengue virus and other arthropod-borne viruses like chikungunya and yellow fever emerge out of non-human primates and into humans. Our study seeks to define the landscape elements, vector species, and primate species that enable these viruses to be transmitted to humans. Moreover we are surveying local people for seroconversion to dengue to assess the frequency and consequences of sylvatic dengue infection.
Southeast Asia: With collaborators at the University of Texas Medical Branch and Universiti Malaysia Sarawak (UNIMAS), we have recently initiated a study of the diversity of arboviruses and vectors in Sarawak, Malaysian Borneo, to better understand the potential for new arboviruses to emerge in this region.
Funding for these projects has been provided by NIH grant 1R01AI069145-01A2, an AAAS Women’s International Collaboration Research grant, a Tulane National Primate Research Center Pilot Study and an NMSU Interdisciplinary Research grant
Hanley, K.A., T.M. Monath, S.C. Weaver, S. L. Rossi, R.L. Richman, N. Vasilakis. 2013. Fever versus Fever: the role of host and vector susceptibility and interspecific competition in shaping the current and future distribution of the sylvatic cycles of dengue virus and yellow fever virus.
Infection, Genetics and Evolution 19:292-311.
Hanley, K.A., M. Guerbois, T. Kautz, M. Brown, S.S. Whitehead S.C. Weaver, N. Vasilakis, P. Marx. 2014. Infection dynamics of sylvatic dengue virus serotype 2 in a natural primate host, the African green monkey. American Journal of Tropical Medicine and Hygiene 91:672-6.
Diallo, D. A.A. Sall, C.T. Diagne, O. Faye, O. Faye, Y. Ba, K.A. Hanley, M. Buenemann, S.C. Weaver, M. Diallo. 2014. Zika virus emergence in mosquitoes in southeastern Senegal, 2011. PLoS One 9(10):e109442
Althouse, B.M., A.P. Durbin, K.A. Hanley, S.B. Halstead, S. C. Weaver, D.A.T. Cummings. 2014. Viral kinetics of primate dengue infection in non-human primates: A systematic review and individual pooled analysis. Virology 452-453: 237-46. PMID: 24606701; PMCID in process. [PDF]
The interaction between arthropod-borne viruses (arboviruses) and the RNA interference (RNAi) response.
In arthropods, the most important defense against infection by arboviruses is RNAi, the targeted destruction of messenger-sense RNA with homology to a double-stranded RNA trigger. In collaboration with the National Center for Genome Resources and with current and former members of Greg Ebel’s lab at Colorado State University, we are characterizing the small RNA response to dengue virus infection in mosquito and mammalian cells in culture and also in different mosquito lines that vary in their susceptibility to dengue virus infection. Additionally, we are investigating how RNAi shapes the evolution of population diversity within hosts (i.e. quasispecies diversity) in West Nile virus and dengue virus.
The figure above shows the size distribution of small RNAs that map to the positive-sense (blue) and negative-sense (red) dengue virus genome in two mammalian (HuH-7 and Vero) and one mosquito (U4.4) cell lines five days post-infection with rDENV-4. Each panel represents the combined virus-derived small RNAs from three independent replicates per cell line. In the left-hand column the Y-axis is scaled to a single standard to represent relative number of virus-derived small RNAs in the three cell lines; in the right-hand column variable Y-axis scales are used to allow visualization of the distribution of virus-derived small RNAs in each cell line. (Schirtzinger et al. 2015)".
This research was supported by a grant from the National Center for Research Resources (5P20RR016480-12), the National Institute of General Medical Sciences (8 P20 GM103451-12), and a competitive pilot award grant from the NM-INBRE Sequencing and Bioinformatics Core at NCGR.
D.E. Brackney, E.E. Schirtzinger, T. Harrison, G.D. Ebel, K.A. Hanley. 2015, in press. Modulation of flavivirus population diversity by RNA interference. Journal of Virology
Schirtzinger, E.E., C.C. Andrade, N. Devitt, T. Ramaraj, J.L. Jacobi, F. Schilkey, K.A. Hanley. 2015. Repertoire of virus-derived small RNAs produced by mosquito and mammalian cells in response to dengue virus infection. Virology 476:54-60
Funding for this study is provided by NIH 1R15AI113628-01
Hanley, K.A., J.T. Nelson, E. E. Schirtzinger, S.S. Whitehead, C.T. Hanson. 2008. Superior infectivity for mosquito vectors contributes to competitive displacement among strains of dengue virus. Biomed Central Ecology 8:1.
Pepin, K.M., K. Lambeth, K.A. Hanley. 2008. Asymmetric competitive suppression between strains of dengue virus. Biomed Central Microbiology 8:28.